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Published in: Current Diabetes Reports 10/2015

01-10-2015 | Pharmacologic Treatment of Type 2 Diabetes (HE Lebovitz and G Bahtiyar, Section Editors)

Targeting Inflammation Through a Physical Active Lifestyle and Pharmaceuticals for the Treatment of Type 2 Diabetes

Authors: Sine Haugaard Knudsen, Bente Klarlund Pedersen

Published in: Current Diabetes Reports | Issue 10/2015

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Abstract

Evidence exists that interleukin (IL)-1β is involved in pancreatic β-cell damage, whereas TNF-α appears to be a key molecule in peripheral insulin resistance. Although increased plasma levels of IL-6 are seen in individuals with type 2 diabetes, mechanistic studies suggest that moderate acute elevations in IL-6, as provoked by exercise, exert anti-inflammatory effects by an inhibition of TNF-α and by stimulating IL-1 receptor antagonist (ra), thereby limiting IL-1β signaling. A number of medical treatments have anti-inflammatory effects. IL-1 antagonists have been tested in clinical studies and appear very promising. Also, there is a potential for anti-TNF-α strategies and salsalate has been shown to improve insulin sensitivity in clinical trials. Furthermore, the anti-inflammatory potential of statins, antagonists of the renin–angiotensin system, and glucose-lowering agents are discussed. While waiting for the outcome of long-term clinical pharmacological trials, it should be emphasized that physical activity represents a natural strong anti-inflammatory intervention with little or no side effects.
Literature
3.
go back to reference Esser N, Legrand-Poels S, Piette J, et al. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105:141–50.PubMedCrossRef Esser N, Legrand-Poels S, Piette J, et al. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105:141–50.PubMedCrossRef
4.
go back to reference Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2014;383:1068–83.PubMedCentralPubMedCrossRef Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2014;383:1068–83.PubMedCentralPubMedCrossRef
6.
go back to reference Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11:98–107.PubMedCrossRef Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11:98–107.PubMedCrossRef
9.
go back to reference Pickup JC, Mattock MB, Chusney GD, et al. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997;40:1286–92.PubMedCrossRef Pickup JC, Mattock MB, Chusney GD, et al. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997;40:1286–92.PubMedCrossRef
10.
go back to reference Spranger J, Kroke A, Mohlig M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003;52:812–7.PubMedCrossRef Spranger J, Kroke A, Mohlig M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003;52:812–7.PubMedCrossRef
11.
go back to reference Herder C, Illig T, Rathmann W, et al. Inflammation and type 2 diabetes: results from KORA Augsburg. Gesundheitswesen. 2005;67 Suppl 1:S115–21.PubMedCrossRef Herder C, Illig T, Rathmann W, et al. Inflammation and type 2 diabetes: results from KORA Augsburg. Gesundheitswesen. 2005;67 Suppl 1:S115–21.PubMedCrossRef
12.
go back to reference Herder C, Brunner EJ, Rathmann W, et al. Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the Whitehall II study. Diabetes Care. 2009;32:421–3.PubMedCentralPubMedCrossRef Herder C, Brunner EJ, Rathmann W, et al. Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the Whitehall II study. Diabetes Care. 2009;32:421–3.PubMedCentralPubMedCrossRef
13.
go back to reference Pedersen M, Bruunsgaard H, Weis N, et al. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev. 2003;124:495–502.PubMedCrossRef Pedersen M, Bruunsgaard H, Weis N, et al. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev. 2003;124:495–502.PubMedCrossRef
14.
go back to reference Plomgaard P, Nielsen AR, Fischer CP, et al. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes. Diabetologia. 2007;50:2562–71.PubMedCrossRef Plomgaard P, Nielsen AR, Fischer CP, et al. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes. Diabetologia. 2007;50:2562–71.PubMedCrossRef
15.
go back to reference Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286:327–34.PubMedCrossRef Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286:327–34.PubMedCrossRef
16.
go back to reference Carstensen M, Herder C, Kivimaki M, et al. Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes. 2010;59:1222–7.PubMedCentralPubMedCrossRef Carstensen M, Herder C, Kivimaki M, et al. Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes. 2010;59:1222–7.PubMedCentralPubMedCrossRef
17.
go back to reference Eguchi K, Manabe I. Macrophages and islet inflammation in type 2 diabetes. Diabetes Obes Metab. 2013;15 Suppl 3:152–8.PubMedCrossRef Eguchi K, Manabe I. Macrophages and islet inflammation in type 2 diabetes. Diabetes Obes Metab. 2013;15 Suppl 3:152–8.PubMedCrossRef
18.
go back to reference Ehses JA, Perren A, Eppler E, et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes. 2007;56:2356–70.PubMedCrossRef Ehses JA, Perren A, Eppler E, et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes. 2007;56:2356–70.PubMedCrossRef
19.
go back to reference Westwell-Roper CY, Ehses JA, Verchere CB. Resident macrophages mediate islet amyloid polypeptide-induced islet IL-1beta production and beta-cell dysfunction. Diabetes. 2014;63:1698–711.PubMedCrossRef Westwell-Roper CY, Ehses JA, Verchere CB. Resident macrophages mediate islet amyloid polypeptide-induced islet IL-1beta production and beta-cell dysfunction. Diabetes. 2014;63:1698–711.PubMedCrossRef
20.
go back to reference Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356:1517–26.PubMedCrossRef Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356:1517–26.PubMedCrossRef
21.
go back to reference Hotamisligil GS, Peraldi P, Budavari A, et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.PubMedCrossRef Hotamisligil GS, Peraldi P, Budavari A, et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.PubMedCrossRef
22.
go back to reference Uysal KT, Wiesbrock SM, Marino MW, et al. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610–4.PubMedCrossRef Uysal KT, Wiesbrock SM, Marino MW, et al. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610–4.PubMedCrossRef
23.
go back to reference Plomgaard P, Bouzakri K, Krogh-Madsen R, et al. Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. Diabetes. 2005;54:2939–45.PubMedCrossRef Plomgaard P, Bouzakri K, Krogh-Madsen R, et al. Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. Diabetes. 2005;54:2939–45.PubMedCrossRef
24.
go back to reference Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985). 2005;98(4):1154–62. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985). 2005;98(4):1154–62.
25.
go back to reference Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006;16 Suppl 1:3–63.PubMedCrossRef Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006;16 Suppl 1:3–63.PubMedCrossRef
26.•
go back to reference Pedersen BK. Muscle as a secretory organ. Compr Physiol. 2013;3:1337–62. A comprehensive review on the function of the skeletal muscle as a secretory and endocrine organ.PubMed Pedersen BK. Muscle as a secretory organ. Compr Physiol. 2013;3:1337–62. A comprehensive review on the function of the skeletal muscle as a secretory and endocrine organ.PubMed
27.
go back to reference Pedersen BK, Febbraio M. Muscle-derived interleukin-6—a possible link between skeletal muscle, adipose tissue, liver, and brain. Brain Behav Immun. 2005;19:371–6.PubMedCrossRef Pedersen BK, Febbraio M. Muscle-derived interleukin-6—a possible link between skeletal muscle, adipose tissue, liver, and brain. Brain Behav Immun. 2005;19:371–6.PubMedCrossRef
28.••
go back to reference Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol. 2015;11:86–97. A comprehensive review on anti-inflammatory effects of exercise in the context of rheumatic diseases.PubMedCrossRef Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol. 2015;11:86–97. A comprehensive review on anti-inflammatory effects of exercise in the context of rheumatic diseases.PubMedCrossRef
29.
go back to reference Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.PubMedCrossRef Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.PubMedCrossRef
30.
go back to reference Steensberg A, Fischer CP, Keller C, et al. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285:E433–7.PubMedCrossRef Steensberg A, Fischer CP, Keller C, et al. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285:E433–7.PubMedCrossRef
31.
go back to reference Andreasen AS, Krabbe KS, Krogh-Madsen R, et al. Human endotoxemia as a model of systemic inflammation. Curr Med Chem. 2008;15:1697–705.PubMedCrossRef Andreasen AS, Krabbe KS, Krogh-Madsen R, et al. Human endotoxemia as a model of systemic inflammation. Curr Med Chem. 2008;15:1697–705.PubMedCrossRef
32.
go back to reference Starkie R, Ostrowski SR, Jauffred S, et al. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J. 2003;17:884–6.PubMed Starkie R, Ostrowski SR, Jauffred S, et al. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J. 2003;17:884–6.PubMed
33.
go back to reference Schindler R, Mancilla J, Endres S, et al. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990;75:40–7.PubMed Schindler R, Mancilla J, Endres S, et al. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990;75:40–7.PubMed
34.
go back to reference Mizuhara H, O’Neill E, Seki N, et al. T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. J Exp Med. 1994;179:1529–37.PubMedCrossRef Mizuhara H, O’Neill E, Seki N, et al. T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. J Exp Med. 1994;179:1529–37.PubMedCrossRef
35.
go back to reference Ellingsgaard H, Ehses JA, Hammar EB, et al. Interleukin-6 regulates pancreatic alpha-cell mass expansion. Proc Natl Acad Sci U S A. 2008;105:13163–8.PubMedCentralPubMedCrossRef Ellingsgaard H, Ehses JA, Hammar EB, et al. Interleukin-6 regulates pancreatic alpha-cell mass expansion. Proc Natl Acad Sci U S A. 2008;105:13163–8.PubMedCentralPubMedCrossRef
36.
go back to reference Ellingsgaard H, Hauselmann I, Schuler B, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011;17:1481–9.PubMedCentralPubMedCrossRef Ellingsgaard H, Hauselmann I, Schuler B, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011;17:1481–9.PubMedCentralPubMedCrossRef
37.
go back to reference Pischon T, Boeing H, Hoffmann K, et al. General and abdominal adiposity and risk of death in Europe. NEnglJMed. 2008;359:2105–20.CrossRef Pischon T, Boeing H, Hoffmann K, et al. General and abdominal adiposity and risk of death in Europe. NEnglJMed. 2008;359:2105–20.CrossRef
38.
39.
go back to reference Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88:1379–406.PubMedCrossRef Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88:1379–406.PubMedCrossRef
40.
go back to reference Olsen RH, Krogh-Madsen R, Thomsen C, et al. Metabolic responses to reduced daily steps in healthy nonexercising men. JAMA. 2008;299:1261–3.PubMedCrossRef Olsen RH, Krogh-Madsen R, Thomsen C, et al. Metabolic responses to reduced daily steps in healthy nonexercising men. JAMA. 2008;299:1261–3.PubMedCrossRef
41.
go back to reference Krogh-Madsen R, Pedersen M, Solomon TP, et al. Normal physical activity obliterates the deleterious effects of a high-caloric intake. J Appl Physiol (1985). 2014;116:231–9.CrossRef Krogh-Madsen R, Pedersen M, Solomon TP, et al. Normal physical activity obliterates the deleterious effects of a high-caloric intake. J Appl Physiol (1985). 2014;116:231–9.CrossRef
42.
go back to reference Knudsen SH, Hansen LS, Pedersen M, et al. Changes in insulin sensitivity precede changes in body composition during 14 days of step reduction combined with overfeeding in healthy young men. J Appl Physiol (1985). 2012;113:7–15.CrossRef Knudsen SH, Hansen LS, Pedersen M, et al. Changes in insulin sensitivity precede changes in body composition during 14 days of step reduction combined with overfeeding in healthy young men. J Appl Physiol (1985). 2012;113:7–15.CrossRef
43.
go back to reference Donath MY, Storling J, Maedler K, et al. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med (Berl). 2003;81:455–70.CrossRef Donath MY, Storling J, Maedler K, et al. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med (Berl). 2003;81:455–70.CrossRef
44.••
go back to reference Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014;13:465–76. A comprehensive review on anti-inflammatory treatment in type 2 diabetes.PubMedCrossRef Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014;13:465–76. A comprehensive review on anti-inflammatory treatment in type 2 diabetes.PubMedCrossRef
45.
go back to reference Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 2002;110:851–60.PubMedCentralPubMedCrossRef Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 2002;110:851–60.PubMedCentralPubMedCrossRef
46.••
go back to reference Hensen J, Howard CP, Walter V, et al. Impact of interleukin-1beta antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab. 2013;39:524–31. One of the most recent clinical trial testing anti-interleukin-1beta treatment in individuals with type 2 diabetes.PubMedCrossRef Hensen J, Howard CP, Walter V, et al. Impact of interleukin-1beta antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab. 2013;39:524–31. One of the most recent clinical trial testing anti-interleukin-1beta treatment in individuals with type 2 diabetes.PubMedCrossRef
47.
go back to reference Koenen TB, Stienstra R, van Tits LJ, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue. Diabetes. 2011;60:517–24.PubMedCentralPubMedCrossRef Koenen TB, Stienstra R, van Tits LJ, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue. Diabetes. 2011;60:517–24.PubMedCentralPubMedCrossRef
48.
go back to reference Larsen CM, Faulenbach M, Vaag A, et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 2009;32:1663–8.PubMedCentralPubMedCrossRef Larsen CM, Faulenbach M, Vaag A, et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 2009;32:1663–8.PubMedCentralPubMedCrossRef
49.
go back to reference Rissanen A, Howard CP, Botha J, et al. Effect of anti-IL-1beta antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: results of a randomized, placebo-controlled trial. Diabetes Obes Metab. 2012;14:1088–96.PubMedCrossRef Rissanen A, Howard CP, Botha J, et al. Effect of anti-IL-1beta antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: results of a randomized, placebo-controlled trial. Diabetes Obes Metab. 2012;14:1088–96.PubMedCrossRef
50.
go back to reference Sloan-Lancaster J, Abu-Raddad E, Polzer J, et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1beta antibody, in patients with type 2 diabetes. Diabetes Care. 2013;36:2239–46.PubMedCentralPubMedCrossRef Sloan-Lancaster J, Abu-Raddad E, Polzer J, et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1beta antibody, in patients with type 2 diabetes. Diabetes Care. 2013;36:2239–46.PubMedCentralPubMedCrossRef
51.
go back to reference van Asseldonk EJ, Stienstra R, Koenen TB, et al. Treatment with anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2011;96:2119–26.PubMedCrossRef van Asseldonk EJ, Stienstra R, Koenen TB, et al. Treatment with anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2011;96:2119–26.PubMedCrossRef
52.
go back to reference van Poppel PC, van Asseldonk EJ, Holst JJ, et al. The interleukin-1 receptor antagonist anakinra improves first-phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance. Diabetes Obes Metab. 2014;16:1269–73.PubMedCrossRef van Poppel PC, van Asseldonk EJ, Holst JJ, et al. The interleukin-1 receptor antagonist anakinra improves first-phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance. Diabetes Obes Metab. 2014;16:1269–73.PubMedCrossRef
53.
go back to reference Vandanmagsar B, Youm YH, Ravussin A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17:179–88.PubMedCentralPubMedCrossRef Vandanmagsar B, Youm YH, Ravussin A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17:179–88.PubMedCentralPubMedCrossRef
54.
go back to reference Butcher MJ, Hallinger D, Garcia E, et al. Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes. Diabetologia. 2014;57:491–501.PubMedCentralPubMedCrossRef Butcher MJ, Hallinger D, Garcia E, et al. Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes. Diabetologia. 2014;57:491–501.PubMedCentralPubMedCrossRef
55.
go back to reference Boni-Schnetzler M, Thorne J, Parnaud G, et al. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta-cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab. 2008;93:4065–74.PubMedCentralPubMedCrossRef Boni-Schnetzler M, Thorne J, Parnaud G, et al. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta-cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab. 2008;93:4065–74.PubMedCentralPubMedCrossRef
56.
go back to reference Cavelti-Weder C, Babians-Brunner A, Keller C, et al. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. 2012;35:1654–62.PubMedCentralPubMedCrossRef Cavelti-Weder C, Babians-Brunner A, Keller C, et al. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. 2012;35:1654–62.PubMedCentralPubMedCrossRef
57.
go back to reference Ridker PM, Thuren T, Zalewski A, et al. Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597–605.PubMedCrossRef Ridker PM, Thuren T, Zalewski A, et al. Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597–605.PubMedCrossRef
58.
go back to reference Rafiq S, Stevens K, Hurst AJ, et al. Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels. Genes Immun. 2007;8:344–51.PubMedCrossRef Rafiq S, Stevens K, Hurst AJ, et al. Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels. Genes Immun. 2007;8:344–51.PubMedCrossRef
59.
go back to reference Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.PubMedCrossRef Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.PubMedCrossRef
60.
go back to reference Garcia FA, Reboucas JF, Balbino TQ, et al. Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase. J Inflamm (Lond). 2015;12:33.CrossRef Garcia FA, Reboucas JF, Balbino TQ, et al. Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase. J Inflamm (Lond). 2015;12:33.CrossRef
61.
go back to reference Ofei F, Hurel S, Newkirk J, et al. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes. 1996;45:881–5.PubMedCrossRef Ofei F, Hurel S, Newkirk J, et al. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes. 1996;45:881–5.PubMedCrossRef
62.
go back to reference Paquot N, Castillo MJ, Lefebvre PJ, et al. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab. 2000;85:1316–9.PubMed Paquot N, Castillo MJ, Lefebvre PJ, et al. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab. 2000;85:1316–9.PubMed
64.
go back to reference Dominguez H, Storgaard H, Rask-Madsen C, et al. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res. 2005;42:517–25.PubMedCrossRef Dominguez H, Storgaard H, Rask-Madsen C, et al. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res. 2005;42:517–25.PubMedCrossRef
65.
go back to reference Stanley TL, Zanni MV, Johnsen S, et al. TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J Clin Endocrinol Metab. 2011;96:E146–50.PubMedCentralPubMedCrossRef Stanley TL, Zanni MV, Johnsen S, et al. TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J Clin Endocrinol Metab. 2011;96:E146–50.PubMedCentralPubMedCrossRef
66.
go back to reference Navarro JF, Mora C, Muros M, et al. Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial. J Am Soc Nephrol. 2005;16:2119–26.PubMedCrossRef Navarro JF, Mora C, Muros M, et al. Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial. J Am Soc Nephrol. 2005;16:2119–26.PubMedCrossRef
67.
go back to reference Mauer J, Chaurasia B, Goldau J, et al. Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol. 2014;15:423–30.PubMedCentralPubMedCrossRef Mauer J, Chaurasia B, Goldau J, et al. Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol. 2014;15:423–30.PubMedCentralPubMedCrossRef
68.
go back to reference Serrano AL, Baeza-Raja B, Perdiguero E, et al. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2008;7:33–44.PubMedCrossRef Serrano AL, Baeza-Raja B, Perdiguero E, et al. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2008;7:33–44.PubMedCrossRef
69.
70.
go back to reference Carey AL, Lamont B, Andrikopoulos S, et al. Interleukin-6 gene expression is increased in insulin-resistant rat skeletal muscle following insulin stimulation. Biochem Biophys Res Commun. 2003;302:837–40.PubMedCrossRef Carey AL, Lamont B, Andrikopoulos S, et al. Interleukin-6 gene expression is increased in insulin-resistant rat skeletal muscle following insulin stimulation. Biochem Biophys Res Commun. 2003;302:837–40.PubMedCrossRef
71.
go back to reference Wallenius V, Wallenius K, Ahren B, et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med. 2002;8:75–9.PubMedCrossRef Wallenius V, Wallenius K, Ahren B, et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med. 2002;8:75–9.PubMedCrossRef
72.
go back to reference Stouthard JM, Romijn JA, Van der Poll T, et al. Endocrinologic and metabolic effects of interleukin-6 in humans. Am J Physiol. 1995;268:E813–9.PubMed Stouthard JM, Romijn JA, Van der Poll T, et al. Endocrinologic and metabolic effects of interleukin-6 in humans. Am J Physiol. 1995;268:E813–9.PubMed
73.
go back to reference Tsigos C, Papanicolaou DA, Kyrou I, et al. Dose-dependent effects of recombinant human interleukin-6 on glucose regulation. J Clin Endocrinol Metab. 1997;82:4167–70.PubMedCrossRef Tsigos C, Papanicolaou DA, Kyrou I, et al. Dose-dependent effects of recombinant human interleukin-6 on glucose regulation. J Clin Endocrinol Metab. 1997;82:4167–70.PubMedCrossRef
74.
go back to reference Steensberg A, Fischer CP, Sacchetti M, et al. Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans. J Physiol. 2003;548:631–8.PubMedCentralPubMedCrossRef Steensberg A, Fischer CP, Sacchetti M, et al. Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans. J Physiol. 2003;548:631–8.PubMedCentralPubMedCrossRef
75.
go back to reference Carey AL, Steinberg GR, Macaulay SL, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. 2006;55:2688–97.PubMedCrossRef Carey AL, Steinberg GR, Macaulay SL, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. 2006;55:2688–97.PubMedCrossRef
76.
go back to reference Harder-Lauridsen NM, Krogh-Madsen R, Holst JJ, et al. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2014;306:E769–78.PubMedCrossRef Harder-Lauridsen NM, Krogh-Madsen R, Holst JJ, et al. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2014;306:E769–78.PubMedCrossRef
77.
78.
go back to reference Scheele C, Nielsen S, Kelly M, et al. Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6. PLoS One. 2012;7:e39657. 1–10.PubMedCentralPubMedCrossRef Scheele C, Nielsen S, Kelly M, et al. Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6. PLoS One. 2012;7:e39657. 1–10.PubMedCentralPubMedCrossRef
79.
go back to reference Febbraio MA, Rose-John S, Pedersen BK. Is interleukin-6 receptor blockade the Holy Grail for inflammatory diseases? Clin Pharmacol Ther. 2010;87:396–8.PubMedCrossRef Febbraio MA, Rose-John S, Pedersen BK. Is interleukin-6 receptor blockade the Holy Grail for inflammatory diseases? Clin Pharmacol Ther. 2010;87:396–8.PubMedCrossRef
80.
go back to reference Nishimoto N. Clinical studies in patients with Castleman’s disease, Crohn’s disease, and rheumatoid arthritis in Japan. Clin Rev Allergy Immunol. 2005;28:221–30.PubMedCrossRef Nishimoto N. Clinical studies in patients with Castleman’s disease, Crohn’s disease, and rheumatoid arthritis in Japan. Clin Rev Allergy Immunol. 2005;28:221–30.PubMedCrossRef
81.•
go back to reference Goldfine AB, Fonseca V, Jablonski KA, et al. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2013;159:1–12. The most recent clinical trial testing salsalate in individuals with type 2 diabetes.PubMedCentralPubMedCrossRef Goldfine AB, Fonseca V, Jablonski KA, et al. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2013;159:1–12. The most recent clinical trial testing salsalate in individuals with type 2 diabetes.PubMedCentralPubMedCrossRef
82.
go back to reference Fleischman A, Shoelson SE, Bernier R, et al. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008;31:289–94.PubMedCentralPubMedCrossRef Fleischman A, Shoelson SE, Bernier R, et al. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008;31:289–94.PubMedCentralPubMedCrossRef
83.
go back to reference Goldfine AB, Silver R, Aldhahi W, et al. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci. 2008;1:36–43.PubMedCentralPubMedCrossRef Goldfine AB, Silver R, Aldhahi W, et al. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci. 2008;1:36–43.PubMedCentralPubMedCrossRef
84.
go back to reference Koska J, Ortega E, Bunt JC, et al. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia. 2009;52:385–93.PubMedCentralPubMedCrossRef Koska J, Ortega E, Bunt JC, et al. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia. 2009;52:385–93.PubMedCentralPubMedCrossRef
85.
go back to reference Yuan M, Konstantopoulos N, Lee J, et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science. 2001;293:1673–7.PubMedCrossRef Yuan M, Konstantopoulos N, Lee J, et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science. 2001;293:1673–7.PubMedCrossRef
86.
go back to reference Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337–42.PubMedCrossRef Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337–42.PubMedCrossRef
87.
go back to reference Timmers S, Konings E, Bilet L, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14:612–22.PubMedCrossRef Timmers S, Konings E, Bilet L, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14:612–22.PubMedCrossRef
88.
go back to reference Tome-Carneiro J, Larrosa M, Yanez-Gascon MJ, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69–82.PubMedCrossRef Tome-Carneiro J, Larrosa M, Yanez-Gascon MJ, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69–82.PubMedCrossRef
89.
go back to reference Zagotta I, Dimova EY, Debatin KM, et al. Obesity and inflammation: reduced cytokine expression due to resveratrol in a human in vitro model of inflamed adipose tissue. Front Pharmacol. 2015;6:79. 1–10.PubMedCentralPubMedCrossRef Zagotta I, Dimova EY, Debatin KM, et al. Obesity and inflammation: reduced cytokine expression due to resveratrol in a human in vitro model of inflamed adipose tissue. Front Pharmacol. 2015;6:79. 1–10.PubMedCentralPubMedCrossRef
90.
go back to reference Poulsen MM, Vestergaard PF, Clasen BF, et al. High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes. 2013;62:1186–95.PubMedCentralPubMedCrossRef Poulsen MM, Vestergaard PF, Clasen BF, et al. High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes. 2013;62:1186–95.PubMedCentralPubMedCrossRef
91.
go back to reference Olesen J, Gliemann L, Bienso R, et al. Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. J Physiol. 2014;592:1873–86.PubMedCentralPubMedCrossRef Olesen J, Gliemann L, Bienso R, et al. Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. J Physiol. 2014;592:1873–86.PubMedCentralPubMedCrossRef
92.
go back to reference Gliemann L, Schmidt JF, Olesen J, et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol. 2013;591:5047–59.PubMedCentralPubMedCrossRef Gliemann L, Schmidt JF, Olesen J, et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol. 2013;591:5047–59.PubMedCentralPubMedCrossRef
93.•
go back to reference Scheen AJ, Esser N, Paquot N. Antidiabetic agents: potential anti-inflammatory activity beyond glucose control. Diabetes Metab. 2015. doi:10.1016/j.diabet.2015.02.003. A comprehensive review on anti-inflammatory effects of glucose-lowering treatment in type 2 diabetes. Scheen AJ, Esser N, Paquot N. Antidiabetic agents: potential anti-inflammatory activity beyond glucose control. Diabetes Metab. 2015. doi:10.​1016/​j.​diabet.​2015.​02.​003. A comprehensive review on anti-inflammatory effects of glucose-lowering treatment in type 2 diabetes.
95.
go back to reference Ferdaoussi M, Abdelli S, Yang JY, et al. Exendin-4 protects beta-cells from interleukin-1 beta-induced apoptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes. 2008;57:1205–15.PubMedCrossRef Ferdaoussi M, Abdelli S, Yang JY, et al. Exendin-4 protects beta-cells from interleukin-1 beta-induced apoptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes. 2008;57:1205–15.PubMedCrossRef
97.
go back to reference Omar BA, Vikman J, Winzell MS, et al. Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin in an advanced-aged diet-induced obesity mouse model. Diabetologia. 2013;56:1752–60.PubMedCrossRef Omar BA, Vikman J, Winzell MS, et al. Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin in an advanced-aged diet-induced obesity mouse model. Diabetologia. 2013;56:1752–60.PubMedCrossRef
98.
go back to reference Pugazhenthi U, Velmurugan K, Tran A, et al. Anti-inflammatory action of exendin-4 in human islets is enhanced by phosphodiesterase inhibitors: potential therapeutic benefits in diabetic patients. Diabetologia. 2010;53:2357–68.PubMedCrossRef Pugazhenthi U, Velmurugan K, Tran A, et al. Anti-inflammatory action of exendin-4 in human islets is enhanced by phosphodiesterase inhibitors: potential therapeutic benefits in diabetic patients. Diabetologia. 2010;53:2357–68.PubMedCrossRef
99.•
go back to reference Hogan AE, Gaoatswe G, Lynch L, et al. Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus. Diabetologia. 2014;57:781–4. Anti-inflammatory effects of glucagon-like peptide 1 analogue therapy in individuals with type 2 diabetes.PubMedCrossRef Hogan AE, Gaoatswe G, Lynch L, et al. Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus. Diabetologia. 2014;57:781–4. Anti-inflammatory effects of glucagon-like peptide 1 analogue therapy in individuals with type 2 diabetes.PubMedCrossRef
100.
go back to reference Diaz-Delfin J, Morales M, Caelles C. Hypoglycemic action of thiazolidinediones/peroxisome proliferator-activated receptor gamma by inhibition of the c-Jun NH2-terminal kinase pathway. Diabetes. 2007;56:1865–71.PubMedCrossRef Diaz-Delfin J, Morales M, Caelles C. Hypoglycemic action of thiazolidinediones/peroxisome proliferator-activated receptor gamma by inhibition of the c-Jun NH2-terminal kinase pathway. Diabetes. 2007;56:1865–71.PubMedCrossRef
101.
go back to reference Isoda K, Young JL, Zirlik A, et al. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol. 2006;26:611–7.PubMedCrossRef Isoda K, Young JL, Zirlik A, et al. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol. 2006;26:611–7.PubMedCrossRef
103.
go back to reference Stocker DJ, Taylor AJ, Langley RW, et al. A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes. Am Heart J. 2007;153:445–6.PubMedCrossRef Stocker DJ, Taylor AJ, Langley RW, et al. A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes. Am Heart J. 2007;153:445–6.PubMedCrossRef
105.
go back to reference Derosa G, Cicero AF, Fogari E, et al. Pioglitazone compared to glibenclamide on lipid profile and inflammation markers in type 2 diabetic patients during an oral fat load. Horm Metab Res. 2011;43:505–12.PubMedCrossRef Derosa G, Cicero AF, Fogari E, et al. Pioglitazone compared to glibenclamide on lipid profile and inflammation markers in type 2 diabetic patients during an oral fat load. Horm Metab Res. 2011;43:505–12.PubMedCrossRef
106.
go back to reference Schondorf T, Musholt PB, Hohberg C, et al. The fixed combination of pioglitazone and metformin improves biomarkers of platelet function and chronic inflammation in type 2 diabetes patients: results from the PIOfix study. J Diabetes Sci Technol. 2011;5:426–32.PubMedCentralPubMedCrossRef Schondorf T, Musholt PB, Hohberg C, et al. The fixed combination of pioglitazone and metformin improves biomarkers of platelet function and chronic inflammation in type 2 diabetes patients: results from the PIOfix study. J Diabetes Sci Technol. 2011;5:426–32.PubMedCentralPubMedCrossRef
107.
go back to reference Tung D, Cheung PH, Ciallella J, et al. Novel anti-inflammatory effects of repaglinide in rodent models of inflammation. Pharmacology. 2011;88:295–301.PubMedCrossRef Tung D, Cheung PH, Ciallella J, et al. Novel anti-inflammatory effects of repaglinide in rodent models of inflammation. Pharmacology. 2011;88:295–301.PubMedCrossRef
108.
go back to reference Derosa G, Maffioli P, Ferrari I, et al. Acarbose actions on insulin resistance and inflammatory parameters during an oral fat load. Eur J Pharmacol. 2011;651:240–50.PubMedCrossRef Derosa G, Maffioli P, Ferrari I, et al. Acarbose actions on insulin resistance and inflammatory parameters during an oral fat load. Eur J Pharmacol. 2011;651:240–50.PubMedCrossRef
109.
go back to reference van der Zijl NJ, Moors CC, Goossens GH, et al. Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms. Diabetes Obes Metab. 2012;14:586–95.PubMedCrossRef van der Zijl NJ, Moors CC, Goossens GH, et al. Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms. Diabetes Obes Metab. 2012;14:586–95.PubMedCrossRef
110.
go back to reference Jandeleit-Dahm KA, Tikellis C, Reid CM, et al. Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens. 2005;23:463–73.PubMedCrossRef Jandeleit-Dahm KA, Tikellis C, Reid CM, et al. Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens. 2005;23:463–73.PubMedCrossRef
111.
go back to reference Fujisaka S, Usui I, Kanatani Y, et al. Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice. Endocrinology. 2011;152:1789–99.PubMedCrossRef Fujisaka S, Usui I, Kanatani Y, et al. Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice. Endocrinology. 2011;152:1789–99.PubMedCrossRef
112.
go back to reference Manabe S, Okura T, Watanabe S, et al. Effects of angiotensin II receptor blockade with valsartan on pro-inflammatory cytokines in patients with essential hypertension. J Cardiovasc Pharmacol. 2005;46:735–9.PubMedCrossRef Manabe S, Okura T, Watanabe S, et al. Effects of angiotensin II receptor blockade with valsartan on pro-inflammatory cytokines in patients with essential hypertension. J Cardiovasc Pharmacol. 2005;46:735–9.PubMedCrossRef
113.
go back to reference Pavlatou MG, Mastorakos G, Margeli A, et al. Angiotensin blockade in diabetic patients decreases insulin resistance-associated low-grade inflammation. Eur J Clin Invest. 2011;41:652–8.PubMedCrossRef Pavlatou MG, Mastorakos G, Margeli A, et al. Angiotensin blockade in diabetic patients decreases insulin resistance-associated low-grade inflammation. Eur J Clin Invest. 2011;41:652–8.PubMedCrossRef
114.
go back to reference Feldman M, Jialal I, Devaraj S, et al. Effects of low-dose aspirin on serum C-reactive protein and thromboxane B2 concentrations: a placebo-controlled study using a highly sensitive C-reactive protein assay. J Am Coll Cardiol. 2001;37:2036–41.PubMedCrossRef Feldman M, Jialal I, Devaraj S, et al. Effects of low-dose aspirin on serum C-reactive protein and thromboxane B2 concentrations: a placebo-controlled study using a highly sensitive C-reactive protein assay. J Am Coll Cardiol. 2001;37:2036–41.PubMedCrossRef
115.
go back to reference Ridker PM, Rifai N, Pfeffer MA, et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100:230–5.PubMedCrossRef Ridker PM, Rifai N, Pfeffer MA, et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100:230–5.PubMedCrossRef
116.
go back to reference Jialal I, Miguelino E, Griffen SC, et al. Concomitant reduction of low-density lipoprotein-cholesterol and biomarkers of inflammation with low-dose simvastatin therapy in patients with type 1 diabetes. J Clin Endocrinol Metab. 2007;92:3136–40.PubMedCentralPubMedCrossRef Jialal I, Miguelino E, Griffen SC, et al. Concomitant reduction of low-density lipoprotein-cholesterol and biomarkers of inflammation with low-dose simvastatin therapy in patients with type 1 diabetes. J Clin Endocrinol Metab. 2007;92:3136–40.PubMedCentralPubMedCrossRef
117.
go back to reference Erikstrup C, Ullum H, Pedersen BK. Short-term simvastatin treatment has no effect on plasma cytokine response in a human in vivo model of low-grade inflammation. Clin Exp Immunol. 2006;144:94–100.PubMedCentralPubMedCrossRef Erikstrup C, Ullum H, Pedersen BK. Short-term simvastatin treatment has no effect on plasma cytokine response in a human in vivo model of low-grade inflammation. Clin Exp Immunol. 2006;144:94–100.PubMedCentralPubMedCrossRef
118.
go back to reference Coward WR, Marei A, Yang A, et al. Statin-induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes. J Immunol. 2006;176:5284–92.PubMedCrossRef Coward WR, Marei A, Yang A, et al. Statin-induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes. J Immunol. 2006;176:5284–92.PubMedCrossRef
119.
go back to reference Kuijk LM, Mandey SH, Schellens I, et al. Statin synergizes with LPS to induce IL-1beta release by THP-1 cells through activation of caspase-1. Mol Immunol. 2008;45:2158–65.PubMedCrossRef Kuijk LM, Mandey SH, Schellens I, et al. Statin synergizes with LPS to induce IL-1beta release by THP-1 cells through activation of caspase-1. Mol Immunol. 2008;45:2158–65.PubMedCrossRef
120.
go back to reference Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.PubMedCrossRef Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.PubMedCrossRef
121.
go back to reference Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735–42.PubMedCrossRef Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735–42.PubMedCrossRef
Metadata
Title
Targeting Inflammation Through a Physical Active Lifestyle and Pharmaceuticals for the Treatment of Type 2 Diabetes
Authors
Sine Haugaard Knudsen
Bente Klarlund Pedersen
Publication date
01-10-2015
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 10/2015
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-015-0642-1

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